Auditory Brainstem Implantation in Young Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Auditory Brainstem Implantation in Young Children (NCT01904448), a na na study. The primary outcome is Number of ABI Complications.

2. Clinical Question

The study asks whether auditory brainstem implantation can be used safely in young children who have cochlear or cochlear nerve disorders that prevent cochlear implantation or have not benefited adequately from it. The registry describes children without neurofibromatosis type II and names developmental or acquired cochlear nerve deficiency, cochlear aplasia, post-meningitis cochlear ossification, and cochlear malformation among the relevant conditions. The study also sought preliminary information about sound awareness, speech understanding, and oral language after implantation.

The intended evidence is preliminary feasibility evidence, not a controlled estimate of the implant’s effect relative to another treatment. The registry’s aims include safety, tolerance of stimulation, and possible auditory and language development. Those aims are broader than the primary endpoint, which counts complications. The listed secondary measures include standardized language, articulation, communication-development, and speech-production assessments. The registry record does not report results for those measures, so the clinical question about auditory or language change cannot be answered from the results described in the record.

3. Trial Design

This is a completed, single-group device study of auditory brainstem implantation in children. The registry lists enrollment as 5 and describes the intervention as implantation of an auditory brainstem implant. Allocation is listed as NA, masking as none, and phase as NA. A concurrent randomized comparison is not described. The study was sponsored by the University of North Carolina, Chapel Hill.

The registry gives a start date of 2012-09 and a primary completion date of 2017-10-01. Its summary says the study proposed to implant up to 10 young children, while the enrollment field records 5. The record therefore distinguishes the proposed upper enrollment from the recorded enrollment; neither figure should be mistaken for the number contributing to a particular endpoint, because endpoint-specific analysis counts are not reported.

The population was children with cochlear or cochlear nerve disorders not resulting from neurofibromatosis type II. The rationale described in the study summary was that some children had experienced failed cochlear implantation or could not receive cochlear implantation because of their underlying disorder. The intervention is a device procedure, rather than a drug regimen, and the study aimed to assess surgical safety, tolerance of stimulation, and potential auditory benefit.

Because there is no parallel control arm, changes in a participant’s skills from baseline would not by themselves establish that the implant caused the change. Development, prior cochlear-implant experience, underlying diagnosis, and other differences could also matter, but the registry does not report information that would allow those influences to be assessed. The registry record does not report a detailed statistical analysis plan, a sample-size justification, or an interim-analysis plan. It also does not report outcome-level participant counts or results for the language and auditory measures.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of ABI Complications, measured over Year 3.

The primary endpoint is the number of ABI complications, measured in events, with a timeframe of Year 3. The description says complications and related outcomes are to be tracked and recorded. Examples include bleeding, infection, neural injury, cerebrospinal fluid leakage, brain bleeding or bruising, stroke, and death. Device-related complications, including non-auditory stimulation and device failure, are also included.

A complication count is a safety-focused endpoint. It can describe the burden of recorded events over the stated follow-up timeframe and can help characterize the kinds of problems observed during a feasibility study. It is not the same as a measure of how many participants experienced at least one complication: a participant may experience more than one event, and the registry’s primary endpoint is expressed as events. Nor does an event count alone describe its severity, duration, consequences, or relationship to the procedure or device.

The registry record identifies the endpoint and timeframe but does not report the primary endpoint’s results or an analysis. It is therefore not possible to describe the recorded Year 3 complication count from the primary endpoint information. The separate adverse-event summary reports serious-event information, but it should not be treated as a substitute for the complete primary endpoint result, since the endpoint description includes a broader set of complications and related outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on the design and the form of the endpoint. This is a single-group study, and its primary endpoint is an event count. The registry reports a serious-event summary but lists 0 analyses. The following concepts explain how such evidence is generally read; they are not a claim that the registry used a particular statistical method.

What does a single-group design allow?

In a single-group design, the observations describe participants who received the study intervention. There is no concurrent comparison group to estimate what would have happened under an alternative intervention or under usual care. If an outcome is measured at baseline and again after treatment, the within-participant change can be described, but it does not automatically isolate the treatment effect. Natural development, changing circumstances, prior treatment, measurement variation, and selection of participants can all contribute to observed change.

Random allocation in a comparative study helps balance known and unknown factors between groups on average. Here, allocation is listed as NA and the study model is single-group. That means randomized between-group contrasts are not part of the design described in the registry. A comparison with baseline, mentioned in the study aims, is not equivalent to a randomized control comparison.

Why does the endpoint’s form matter?

An event count records how many events occur, rather than directly recording the proportion of participants with an event. Counts may reflect multiple events in an individual, and interpretation depends on how events are defined, collected, and attributed. A count can also depend on the length and completeness of follow-up. The registry specifies Year 3 as the primary endpoint timeframe, but it does not report detailed follow-up completeness or the endpoint count.

In general, counts may be analyzed using methods suited to count data. A Poisson model is one common approach when its assumptions are appropriate. Count data can show over-dispersion when variability exceeds what a basic Poisson model expects; in that situation, a model that allows extra variability may be considered. These are general methodological points only. The registry record does not report which model, if any, was used, whether over-dispersion was assessed, or whether the primary count was analyzed at all.

How should estimates and uncertainty be read?

An estimate describes the result in the observed study data. A confidence interval is a range generated by a statistical procedure that conveys uncertainty about an estimate under that procedure’s assumptions. Narrower intervals generally indicate greater precision, while wider intervals indicate less precision. A confidence interval does not guarantee that the true value lies within the reported interval, and its interpretation depends on the study design and method. The registry record does not report confidence intervals for the primary or secondary outcomes.

For a small feasibility study, estimates can be unstable, especially for uncommon events or outcomes with incomplete observations. A point estimate alone would not show how much uncertainty surrounds it. Conversely, a small number of observed events should not be interpreted as proof that a complication cannot occur. The reported serious-event figures are descriptive; no inferential comparison, interval estimate, or adjusted analysis is reported.

What does the absence of analysis information mean?

The registry lists 19 outcome measures and 0 analyses. This means the record identifies multiple outcomes but does not provide analyses for them in its analysis listing. It does not establish that no analyses were conducted outside the registry; it means they are not reported in the registry record. The record also does not describe a statistical analysis plan, any covariate adjustments, or how repeated measurements were handled.

For language and speech assessments, general analysis choices could include describing scores over time, estimating within-participant changes, or modeling repeated measurements. Those approaches require information about the measurement schedule, participant-level data, missing observations, and the analysis objective. The registry record does not report these details or outcome results. It would therefore be inappropriate to infer a method or supply an effect estimate.

Sample-size planning and observed evidence are also distinct. A planning calculation describes how much information a future design might need under stated assumptions; it does not describe the observed effect or the actual precision of this study. No sample-size justification is reported in the registry record. Similarly, a power calculation based on an observed effect would not be observed power and could not replace an estimate with an uncertainty interval. The record does not report a protocol-specific sample-size rationale or an interim-analysis plan.

Why is a comparator important?

Comparative methods require a clearly defined contrast. In a randomized trial, the contrast between assigned groups can support an estimate of the effect of assignment, subject to issues such as adherence, missing outcomes, and measurement quality. A single-group study has no randomized contrast. Comparing a participant’s post-implant result with baseline can be informative for feasibility and description, but it does not eliminate time-related changes or other explanations. The registry’s safety summary should therefore be understood as an account of events among enrolled participants, not as an estimate of excess risk relative to a comparator.

Overall, the methods information needed for an inferential interpretation is not reported in the registry record. The design and endpoint are identifiable, but analysis methods, endpoint results, uncertainty estimates, and outcome-specific populations are absent. General statistical concepts can clarify what those missing elements would contribute, but cannot supply results that the record does not report.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures, including a primary complication-count endpoint and secondary language, articulation, communication, and speech-production measures. When a study evaluates many outcomes, the chance of finding at least one apparently notable result by chance can increase if each is tested separately without accounting for multiplicity. General approaches include naming a primary endpoint in advance, specifying a hierarchy of tests, or adjusting inference across a family of outcomes. The registry record does not report a multiplicity strategy or a statistical analysis plan, so it is not possible to determine how multiple outcomes were intended to be interpreted.

The record lists 0 analyses and does not report results for the named secondary outcomes. It also does not report whether all enrolled participants completed each assessment, how missing measurements were handled, or whether analyses used all enrolled participants or a defined subset. Those details matter because missingness can affect both the apparent outcome and the population to which results apply. If participants with particular outcomes are more likely to have missing data, a complete-case summary may not represent the whole enrolled group.

For repeated language or speech assessments, general analysis choices depend on when measurements were scheduled, whether observations are paired within participants, and how incomplete follow-up is addressed. The registry record does not report those design or analysis details. It also does not report outcome-specific denominators, so the enrollment figure cannot be assumed to describe the participants contributing to every listed measure.

These gaps limit interpretation, but they do not establish that outcomes were not collected or that no analysis occurred outside the registry. They establish only that multiplicity handling, missing-data methods, and analysis populations are not reported in the registry record. No inference about efficacy should be drawn from outcome names alone.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: cerebral spinal fluid (csf) leak (20.0%), aseptic meningitis (20.0%).

The serious adverse-event summary lists the Pediatric ABI group with 5 participants at risk and 2 affected by serious events. It lists 0 affected by other events and 0 deaths. The serious-event terms shown are Cerebral Spinal Fluid (CSF) Leak at 20.0% and Aseptic Meningitis at 20.0%. These are descriptive registry summaries, not a comparison with another treatment group.

The event terms and the number affected answer different questions. The participant figure indicates how many were recorded as affected by serious events, while the terms identify reported event categories. The percentages are presented as part of the registry’s term summary and should not be treated as evidence of a causal relationship or as a complete clinical account. The record does not report event timing, duration, outcomes, attribution, or whether an individual could contribute to more than one event category.

Zero deaths in this summary means no deaths are recorded in this group’s adverse-event summary. It does not show that all possible harms were absent. The primary endpoint includes a broader set of complications and related device outcomes, and its Year 3 event count is not reported in the registry record. The serious-event figures should therefore be read alongside the endpoint description, without substituting them for a complete complication analysis.

12. What the Result Does, and Does Not, Mean

The record describes a feasibility study of auditory brainstem implantation in children with cochlear or cochlear nerve disorders. It provides the study’s intended safety and developmental aims, identifies the primary complication-count endpoint, and reports a limited serious adverse-event summary. It also records enrollment as 5 and labels the study completed. Those details describe the scope and status of the study, not the size of an implant effect.

The available safety summary reports 2 participants affected by serious events, 0 affected by other events, and 0 deaths among 5 at risk. It also lists CSF leak and aseptic meningitis as serious-event terms, each at 20.0%. These descriptive entries can inform awareness of events recorded in the study. They do not establish the comparative risk of the procedure or device, because there is no concurrent control group and no comparative analysis is reported.

The registry’s central efficacy-related aims concern sound awareness, speech understanding, and oral language. It names several relevant assessments, including listening comprehension, oral expression, articulation, and communication-development measures. However, the registry record reports 0 analyses and does not report results for these measures. The primary complication-count result is also not reported in the registry record. Thus, the record does not support a conclusion about the amount of auditory or language change, its precision, or whether any observed change was attributable to implantation.

The study’s feasibility purpose is important when considering what can reasonably be inferred. Preliminary experience can help characterize procedures, outcomes to measure, and issues to consider in later research. A larger controlled study could address comparative questions more directly, but the registry record does not report a plan or protocol for such a study. The record should not be read as demonstrating that the intervention works or does not work. Its reported information is descriptive and incomplete for estimating efficacy or comparative safety.

13. Why This Trial Matters Statistically

This study raises an important statistical challenge: evaluating a device procedure in a population for whom conventional cochlear implantation may not be possible or may have failed. The registry’s single-group feasibility design can document the experience of the enrolled children, including complications and the intended auditory and language measures. It is a useful design for describing early clinical experience, but it cannot by itself provide a randomized estimate of treatment effect.

The distinction between the study’s broad aims and its primary endpoint is also statistically important. The primary endpoint counts complications through Year 3, while the stated developmental aims involve sound awareness, speech understanding, and oral language. These questions require different outcome definitions and analyses. A complication count does not answer whether language scores changed, and a developmental assessment would not replace systematic safety monitoring.

The record lists 19 outcome measures but 0 analyses. This highlights why prespecifying outcomes and an analysis approach matters when a study assesses multiple domains. Without reported estimates, participant counts by outcome, missing-data handling, and uncertainty measures, readers cannot assess the reliability or precision of developmental findings. These are not merely technical details: they determine how much weight can be placed on a reported change and whether it is interpretable.

Small feasibility studies can identify observed events and support planning for subsequent research, but they provide limited information about rare harms and comparative effectiveness. In this record, the serious-event summary is descriptive and there is no control arm. That limitation does not make the study uninformative; it defines the questions its design can address. The statistical value lies in clearly separating preliminary observation from evidence of comparative benefit or harm.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important limitation for interpretation is the single-group design. With no concurrent randomized comparator, the registry cannot support a direct estimate of how outcomes differ from an alternative treatment or from no auditory brainstem implant. Baseline comparisons, if performed, would remain vulnerable to changes over time and other explanations for observed development.

The enrollment field lists 5, while the study summary describes a proposal to implant up to 10 children. The registry does not report endpoint-specific participant counts, so the number contributing to the primary or secondary outcomes is not established by the enrollment field alone. The record also does not report details of follow-up completeness, timing of individual assessments, or missing-data handling.

Although the primary endpoint is specified as a Year 3 complication count, its result is not reported in the registry record. The registry lists serious-event summaries but does not provide a full event-level account, including timing, duration, attribution, or consequences. The listed secondary measures have no reported analyses, and the record does not report estimates or uncertainty intervals for developmental outcomes.

The record does not report a detailed statistical analysis plan, multiplicity handling, sample-size justification, interim-analysis plan, or analysis populations. It therefore does not allow assessment of whether analyses followed a prespecified approach or whether results are precise. These limitations concern what can be learned from the registry record; they do not establish that information was never collected or analyzed elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Auditory Brainstem Implantation in Young Children — NCT01904448.
• Registry record last updated 2018-07-05; status last verified 2018-02.
• Results first posted 2018-06-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT01904448 is a completed, single-group feasibility study of the Nucleus 24 Multichannel Auditory Brainstem Implant in children with cochlear or cochlear nerve disorders not resulting from neurofibromatosis type II. The registry lists enrollment as 5, with a start date of 2012-09 and primary completion date of 2017-10-01. The primary endpoint is the number of ABI complications at Year 3.

The serious adverse-event summary lists 5 participants at risk, 2 affected by serious events, 0 affected by other events, and 0 deaths. CSF leak and aseptic meningitis are listed at 20.0% each. The record lists 19 outcome measures and 0 analyses. Primary endpoint results, secondary outcome analyses, and detailed statistical methods are not reported in the registry record, limiting conclusions about complications, auditory development, language outcomes, or comparative effects.